1. Field of the Invention
The invention relates to implantable medical devices, one example of which is a stent. More particularly, the invention relates to a method of thermally treating an implantable medical device that includes a polymer, for example, a polymeric coating on the device.
2. Description of the Background
Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating heart disease. A catheter assembly having a balloon portion is introduced percutaneously into the cardiovascular system of a patient via the brachial or femoral artery. The catheter assembly is advanced through the coronary vasculature until the balloon portion is positioned across the occlusive lesion. Once in position across the lesion, the balloon is inflated to a predetermined size to remodel the vessel wall. The balloon is then deflated to a smaller profile to allow the catheter to be withdrawn from the patient's vasculature.
A problem associated with the above procedure includes formation of intimal flaps or torn arterial linings, which can collapse and occlude the conduit after the balloon is deflated. Vasospasms and recoil of the vessel wall also threaten vessel closure. Moreover, thrombosis and restenosis of the artery may develop over several months after the procedure, which may necessitate another angioplasty procedure or a surgical by-pass operation. To reduce the partial or total occlusion of the artery by the collapse of arterial lining and to reduce the chance of the development of thrombosis and restenosis, a stent is implanted in the lumen to maintain the vascular patency.
Stents act as scaffoldings, functioning to physically hold open and, if desired, to expand the wall of the passageway. Typically, stents are capable of being compressed so that they can be inserted through small lumens via catheters and then expanded to a larger diameter once they are at the desired location. Mechanical intervention via stents has reduced the rate of restenosis as compared to balloon angioplasty. Yet, restenosis is still a significant clinical problem with rates ranging from 20-40%. When restenosis does occur in the stented segment, its treatment can be challenging, as clinical options are more limited as compared to lesions that were treated solely with a balloon.
Stents are used not only for mechanical intervention but also as vehicles for providing biological therapy. Biological therapy can be achieved by medicating the stents. Medicated stents provide for the local administration of a therapeutic substance at the diseased site. In order to provide an efficacious concentration to the treated site, systemic administration of such medication often produces adverse or even toxic side effects for the patient. Local delivery is a preferred method of treatment in that smaller total levels of medication are administered in comparison to systemic dosages, but are concentrated at a specific site. Local delivery thus produces fewer side effects and achieves more favorable results.
One proposed method of medicating stents involves the use of a polymeric carrier coated onto the surface of the stent. A composition including a solvent, a polymer dissolved in the solvent, and an active agent dispersed in the blend is applied to the stent by immersing the stent in the composition or by spraying the composition onto the stent. The solvent is allowed to evaporate, leaving on the stent strut surfaces a coating of the polymer and the active agent impregnated in the polymer.
A stent coating can be exposed to significant stress, for example, radial expansion as the stent is deployed. A potential shortcoming of the foregoing method of medicating stents is that the mechanical integrity of a polymeric drug coating can fail in the biological lumen, for example as a result of stress. In some instances, the polymeric coating may have poor adhesion to the surface of the stent. In other instances, if the polymeric coating contains multiple layers of materials, the different layers may not attach well to each other and lack sufficient cohesiveness. Poor cohesion can result if there is inadequate interfacial compatibility between the surface of the stent and the polymer in the coating.
Failure of the mechanical integrity of the polymeric coating while the stent is localized in a patient can lead to a serious risk of embolization because a piece of the polymeric coating can tear or break off from the stent. Polymeric stent coatings having a high drug loading are especially vulnerable to fracture during and after deployment.
It is desirable to provide a polymeric coating that has improved adhesion to the surface of the stent. It also is desirable to improve the cohesion of multiple layers of polymeric material on a stent. Moreover, it is desirable to be able to increase the quantity of the therapeutic substance carried by the polymeric coating without perturbing the mechanical properties of the coating or significantly increasing the thickness of the coating.
Another potential shortcoming of the foregoing method of medicating stents is that the release rate of the active agent may be too high to provide an efficacious treatment. This shortcoming may be especially pronounced with certain active agents. For instance, it has been found that the release rate of 40-O-(2-hydroxy)ethyl-rapamycin from a standard polymeric coating is greater than 50% in about 24 hours. Thus, there is a need for a coating that reduces the release rate of active agents in order to provide a more efficacious release rate profile.
Yet another shortcoming is that there can be significant manufacturing inconsistencies. For instance, there can be release rate variability among different stents. It is believed that when some polymers dry on a stent surface to form a coating, different polymer morphologies can develop for different stent coatings, even if the coating process parameters are consistent. The differences in polymer morphology may cause the release rate of the active agent from the polymeric coatings to vary significantly. As a consequence of the inconsistent release rate profiles among stents, there can be clinical complications. Additionally, when stents are stored, the release rate from the stent coating can change during the storage time, known as “release rate drift.” Thus, there is a need for a method that reduces the variability of the release rate of active agents among stents and over time.
The present invention provides a method and coating to meet the foregoing as well as other needs.